Systematic studies in fibrinolysis (those own systems of the body which are involved in the solubilization of fibrin, the protein from which blood clots are built up) has been hampered by difficulties in manipulating its target substance, fibrin. For further information on the fibrinolytic system see Collen D, 1980, Thrombosis and heamostasis 43: 77-86. The possibilities of replacing, for a model purpose, fibrin, which spontaneously forms a gel, with more easily handled substances, such as casein or albumin, are limited. This is due to the fact that fibrin, except from being the target substance, also has important regulatory functions in the fibrinolytic system. These can not be replaced by model proteins.
The demand for a soluble and hence easily handled fibrin derivative is substantial. Therefore, considerable research efforts have been made in order to satisfy this demand. In 1955, Donelly et al described in Arch. Biochem. Biophys. 56: 369-387, how fibrin can be solubilized in 1 mole/l of NaBr at pH 5.3. Further, in 1976, it was described by Haverkate and Timan in Progress in Chemical Fibrinolysis and Thrombolysis 2: 67-71, that fibrin can be solubilized with 10 mole/l of acetic acid, while in 1982 Ranby et al described in Thrombosis Research 27: 743-749, the solubilization of desAA-fibrin in 3.5 mole/l of urea.
However, neither of these methods has been widely used which confirms that they are not fully satisfactory. Thus, the described methods cause denaturation of the fibrin, which is expressed as a tendency of the fibrin to form, after having been brought back to physiological conditions, a precipitate instead of a gel. Furthermore, the described compositions of soluble fibrin do not stand being frozen/thawed or lyophilized/reconstituted with preserved properties.
As concerns prior art reference is also made to Chem. Abstracts 98 (1983), 69 554, which discloses a retardation of the polymerization of desAA-fibrin and desAABB-fibrin in the presence of Gly-Pro-Arg. However, the present invention is based on the fact that it has very unexpectedly turned out that there is a special type of tetrapeptide which does not only retard but also completely and permanently prevents the polymerization of a certain type of fibrin, viz. desAA-fibrin. This prevention has made it possible to prepare a practical useful preparation of soluble fibrin and even to find completely new areas of applications.
Furthermore, Chem. Abstracts 99 (1983), 118 035, discloses that ".alpha.-chain peptide" inhibits the polymerization of "thrombin-induced fibrin", i.e. desAABB-fibrin. Thus, said article is not relevant in connection with the present invention, according to which the above-mentioned tetrapeptide forms in combination with desAA-fibrin a stable, non-polymerizing composition.
Chem. Abstracts 101 (1984), 106 025, merely discloses that Gly-Pro-Arg-Pro retards the fibrin polymerization by being bound to fibrinopeptide A. Thus, this article is not either relevant in connection with the present invention; see above with reference to C.A. 99 (1983), 118 035.